Multiple myeloma is a disease characterized by the accumulation of a clonal population of terminally differentiated B lymphocytes within the bone marrow. For the vase majority of patients, the disease is incurable and average survival from diagnosis is approximately three years. Attempts to improve upon therapy for multiple myeloma over the last twenty years have resulted in only modest improvements. Due to the lack of success in developing curative therapy for multiple myeloma using currently available treatments, this laboratory is initiating studies designed to provide a better understanding of multiple myeloma biology. We hope that a better understanding of pathogenesis of multiple myeloma will permit the development of novel curative therapies. Studies into the biology of multiple myeloma have thus far failed to identify the molecular basis of the disease. Recently, studies of surface markers in myeloma cells exhibit a consistent pattern of surfacemarker expression distinct from plasma cells. We hypothesize that these differences represent an altered pattern of gene expression resulting from molecular events crucial in multiple myeloma pathogenesis. To test this hypothesis, we propose to compare mRNA expression in myeloma cells and normal plasma cells using the differential technique.